However, RA is neglected in LMICs unquestionably because of gaps in estimates of the burden of disease along with lack of communication strategies informing policy makers around the urgency of the problem [34]

However, RA is neglected in LMICs unquestionably because of gaps in estimates of the burden of disease along with lack of communication strategies informing policy makers around the urgency of the problem [34]. As issues sub-Saharan Africa, potential RA genetic background and environmental risk factors are iMAC2 quite different from those of other parts iMAC2 of the world despite an overall comparable phenotype [4, 14, 36C38]. mice models of collagen-induced arthritis after diesel exhaust particles exposure as well as hypovitaminosis D-related autoimmunity can help understand the role of air pollution in rheumatoid arthritis. All these considerations highlight the necessity to extend high quality epidemiological researches investigating different sources of atmospheric pollution across populations and particularly in low-and-middle countries, in order to further explore the biological plausibility of air flow pollutions effect in the pathogenesis of rheumatoid arthritis. This should be attempted to better inform guidelines aiming to reduce the burden of rheumatoid arthritis. recently analyzed associations between local-scale ambient NO2 and PM2.5 in Calgary, Alberta-Canada, using Land Use Regression models (a favored approach for exposure estimation including individual exposure estimation) and SARDs (SLE, Sjogrens Syndrom, scleroderma, polymyositis, dermatomyositis, or undifferentiated connective tissue disease) [17]. Resultantly, ambient PM2.5 levels but not NO2 are strongly associated iMAC2 with SARDs in Alberta (OR adjusted for age, sex and income?=?1.10, 95?% CI 1.01C1.22). Based on the aforementioned studies and the small amount of data addressing air pollution in relation to RA together with extrapolations from relevant data iMAC2 in other areas, RA could be associated with PM, but also NO2, SO2 and O3 exposures as well. Indeed, PM pollutants are the most harmful tropospheric pollutants for all-cause morbidity and mortality associated with air flow pollutants [19C22]. In addition, they have been associated with other SARDs [15, 17]. Still, they can interact with gaseous pollutants that have been associated with RA [11], and even result from their transformation [22]. Most of all, exposure to diesel exhaust particles (nano PM) during arthritis development exacerbated incidence and severity of RA in mice models of collagen-induced arthritis [23, 24]. However, NO2 and SO2 linked with RA in the EIRA study [11], and O3 linked with risk of RA in the BC study [10] all appear less harmful than PM and their respective concentrations highly depend on their complex interactions. Furthermore, NO2 may essentially serve as a proxy for PM, and O3 increases permeability of the respiratory epithelium to PM, hence exacerbating their actions [22]. Reports on the precise mechanistic link between these specific air flow pollutants and RA are somewhat conflicting. Anyhow, extrapolating from studies on air pollution and respiratory diseases [21, 22] as well as studies on air pollution and other SARDs [15C17] together with knowledge on mechanism of action of tropospheric pollutants [15C24], local lung and systemic oxidative stress and inflammation may be the central underlying mechanism [4, 18, 19, 25, 26]. In particular, free reactive oxygen species released by fine/ultrafine PM or gaseous pollutants inhaled in the respiratory tract are capable of activating nuclear factor ?appa B (NF-?B), a key regulator for pro-inflammatory cytokine production in RA patients [18, 19, 25], leading to excess T helper lymphocyte type1 (Th1) production of tumor necrosis factor alpha, interleukin-1 and interleukin-6 [25]. These cytokines stimulate resting monocytes to mature dendritic cells which then present autoantigens, co-stimulating self-reactive T lymphocytes that migrate to target tissues (preferentially synovial joints), and cause destruction of cells expressing autoantigens [18]. Hence, there is prolonged amplified chronic inflammation, a major prerequisite for protein bounded arginine citrullination and subsequent ACPA production that will later on lead to clinical indicators of RA in genetically susceptible individuals [4, 26]. Moreover, reactive oxygen species per se are capable of worsening RA through induction of periarticular bone erosion [26]. Beyond oxidative stress, air pollution might further contribute to RA development and exacerbation through hypovitaminosis D [27C30]. Remarkably, the link between air pollution and low serum vitamin D has been investigated in astonishingly few cross-sectional studies [31C33]. Agarwal et al. [31] compared serum total 25-hydroxycholecalciferol (25-OH-D)-the best indicator of vitamin D storage- of 34 infants LTBP3 (aged 9C24 months) and toddlers in Mori GateCa highly polluted area- with serum total 25-OH-D of a similar number.